Biomimetic tissue-engineered anterior cruciate ligament replacement

Abstract

There are >200,000 anterior cruciate ligament (ACL) ruptures each year in the United States, and, due to the poor healing properties of the ACL, surgical reconstruction with autograft or allograft tissue is the current treatment of these injuries. To regenerate the ACL, the ideal matrix should be biodegradable, porous, and exhibit sufficient mechanical strength to allow formation of neoligament tissue. Researchers have developed ACL scaffolds with collagen fibers, silk, biodegradable polymers, and composites with limited success. Our group has developed a biomimetic ligament replacement by using 3D braiding technology. In this preliminary in vivo rabbit model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regeneration with our cell-seeded, tissue-engineered ligament replacement.

Fig. 1.

Histology of native ACL and TEL. (A) Rabbit ACL control histological section. (B) Cross-section of entire 12-week unseeded TEL replacement showing thin fibrous capsule, vascularization, and collagen tissue ingrowth. (C) Blood vessel near the edge of the implant. (D) Nonoriented collagen tissue formation at the center of the implant. Weigert's Trichrome stain was used throughout. Red–purple indicates fibroblasts and blood vessels, and blue–green indicates collagen.

Fig. 2.

Sections of 12-week seeded TEL replacement. (A) Cross-section of entire replacement. (B) Cells and collagen tissue encircling the polymer filaments. (C) Cells producing collagen fibrils near the edge of the implant. (D) Sparse cell population and mature collagen ingrowth near the center of the implant. Safranin O stain was used throughout. Red–purple indicates fibroblasts, blue–green indicates collagen, and white circles indicate polymer filaments.

Fig. 3.

Load-deformation graphs measured at 2% per second. (A) Control 5 × 5 PLLA 3D square braids before implantation (unseeded TEL replacement) (B) Four-week unseeded TEL. (C) Twelve-week unseeded TEL. (D) Native rabbit ACL (contralateral legs). (E) Four-week seeded TEL. (F) Twelve-week seeded TEL.

Fig. 4.

TEL replacement, surgical procedure, and mechanical testing. (A) Fibrous hierarchy of 3D 5 × 5 square braid used as a ligament replacement. (B and C) Passage of ligament replacement through the femur bone tunnel. (D) Tension on ligament replacement in grips after removal of surrounding intraarticular tissue and suture buttons before mechanical testing. (E) Twelve-week seeded TEL tensile test to failure after mechanical pullout from the bone.